Streptococcus sanguis interacts with platelets in vitro to induce thrombus-like aggregation. As discovered and characterized by this project, DE 05501, this physiological response of platelets is triggered when plasma membrane receptors bind certain surface determinants on S. sanguis cells. These platelet interactive determinantion S. sanguis include the class I antigen, an adhesin, and the class II antigen a collagen-like immunodeterminant that induces platelet aggregation. Some strains also show sufficient class III activity, a presumptive ecto-ATPase. to amplify the platelet aggregation response by hydrolyzing secreted ATP from the platelet to agonist ADP. Since bacteremias with these strains of S. sanguis occur frequently through life, S. sanguis interactions with platelets in the bloodstream must be considered to be potentially thrombogenic. During the next five years we plan to identify and characterize the specificity for platelets of (i) the class I antigen as an adhesin, (ii) the class II antigen as a receptor-mediated activator and (iii) The class III, ecto-ATPase-like activity. Centra to these studies will be to (iv) isolate and characterize the platelet binding sites and receptors for the class I and II antigens of S. sanguis. We have tentatively identified the latter as GPIa. Our panel of anti- S. sanguis and anti-platelet monoclonal and polyclonal antibodies will be expanded to serve as probes of the respective interactive epitopes. As our data now suggests, (v) we will test in a rabbit model the hypothesis that the platelet contribution to vegetations in subacute bacterial endocarditis (SBE) is due to active thrombotic mechanisms triggered by S. Sanguis. If this hypothesis is confirmed, the role of S. sanguis as an etiological agent in SBE should be considered dichotomous. Adhesion of this bacterium to damaged intracardiac tissues may promote colonization and infection. In addition, S. sanguis may trigger thrombotic growth of the vegetation and thromboembolic sequellae of SBE.